chinmo Is a Functional Effector of the JAK/STAT Pathway that Regulates Eye Development, Tumor Formation, and Stem Cell Self-Renewal in Drosophila

Flaherty, Maria Sol; Salis, Pauline; Evans, Cory J.; Ekas, Laura A.; Marouf, Amine; Zavadil, Jiří; Banerjee, Utpal; Bach, Erika A.

doi:10.1016/j.devcel.2010.02.006

Cited by 177 publications

(249 citation statements)

References 74 publications

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“…Rather, activity of Stat in the germline is essential for continued attachment of GSCs to the hub and retains GSCs in their niche (13). Several lines of evidence suggest that CySCs provide a niche for maintenance of GSCs (13)(14)(15). Consistent with this model, it has been proposed that self-renewal of GSCs is specified by instructive signal(s) from the CySCs, with a likely candidate being TGF-β signaling (13).…”

mentioning

confidence: 60%

Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Lim

Fuller

2012

Proc. Natl. Acad. Sci. U.S.A.

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Adult stem cells are believed to be maintained by a specialized microenvironment, the niche, which provides short-range signals that either instruct stem cells to self-renew or inhibit execution of preprogrammed differentiation pathways. In Drosophila testes, somatic cyst stem cells (CySCs) and the apical hub form the niche for neighboring germline stem cells (GSCs), with CySCs as the proposed source of instructive self-renewal signals [Leatherman JL, Dinardo S (2010) Nat Cell Biol 12(8):806-811]. In contrast to this model, we show that early germ cells with GSC characteristics can be maintained over time after ablation of CySCs and their cyst cell progeny. Without CySCs and cyst cells, early germ cells away from the hub failed to initiate differentiation. Our results suggest that CySCs do not have a necessary instructive role in specifying GSC self-renewal and that the differentiated progeny of CySCs provide an environment necessary to trigger GSC differentiation. This work highlights the complex interaction between different stem cell populations in the same niche and how the state of one stem cell population can influence the fate of the other.

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mentioning

confidence: 60%

Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Lim

Fuller

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…STAT activation in CySCs leads to the expression of zfh-1 [3] and chinmo [4], two factors critical for CySC self-renewal. JAK-STAT signaling does not directly regulate the selfrenewal of GSCs, but governs GSC-niche adhesion [5].…”

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confidence: 99%

Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis

Zhang

Jen³

et al. 2013

Cell Res

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Stem cell niche is a specialized microenvironment crucial for stem cell self-renewal. Drosophila testis contains two types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs), providing a good model for studying niche-stem cell interaction [1]. At the apex of testis tube, non-mitotic somatic cells form a tightly folded structure called the hub. About 10 GSCs, each accompanied by 2 CySCs, make direct contact with the hub cells to form a rose-like structure (Supplementary information, Figure S1A). CySCs rely on the hub cells for niche signals, while GSCs are maintained by niche signals from both the hub cells and CySCs [1].Bone morphogenetic protein (BMP) signaling is critical for GSC maintenance [2], while Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling functions in both CySCs and GSCs. STAT activation in CySCs leads to the expression of zfh-1 [3] and chinmo [4], two factors critical for CySC self-renewal. JAK-STAT signaling does not directly regulate the selfrenewal of GSCs, but governs GSC-niche adhesion [5]. Although Zfh-1 is a direct target of activated STAT, eliminating STAT activity only decreased but did not abolish Zfh-1 expression [3], suggesting that a paralleled pathway(s) may be involved in the regulation of Zfh-1 expression. In the course of immunostaining adult flies expressing a hh enhancer trap, hh-lacZ [6], we observed a strong hh-lacZ staining at the apex of testis (Supplementary information, Figure S1), which is consistent with a previous observation that hh-lacZ was expressed in the hub cells [6], suggesting a potential function of Hedgehog (Hh) signaling in the testis.We examined the expression of several core components of the Hh pathway. Hh is expressed in the hub cells as revealed by hh-lacZ and Hh stainings (Supplementary information, Figure S1), which is consistent with a recent finding from Michel M et al. [7]. The stainings of Ci-lacZ, Ci, ptc-lacZ and Smo largely coincide with that of Zfh-1 expression (Supplementary information, Figure S1). Immunostainings and real-time PCR analyses strongly suggest that Ci, Ptc and Smo are enriched in cyst cells (Supplementary information, Figure S1 and Data S1). We used different approaches to activate or inactivate Hh signaling and used Ptc expression as a readout of Hh pathway activity, as Ptc itself is a target of Hh signaling. The results strongly argue for the presence of a functional Hh pathway in Drosophila testis (Supplementary information, Figure S2).To test whether Hh signaling functions in CySCs, we quantified the number of CySCs by calculating Zfh- 1-positive cells under different Hh signaling activities (Supplementary information, Data S1). Smo RNAi, CiRNAi or the ectopic expression of Smo PKA123 (Smo dominant negative form) driven by cyst cell-specific c587-Gal4 significantly reduced CySC number, whereas the expression of Smo SD123 (Smo active form) in cyst cells significantly increased CySC number ( Figure 1A). By contrast, knockdown of Ci or Smo using RNAi driven by germlin...

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“…But few cells like hematopoietic, dendrocytes, Kupffer doi: 10.7243/2050-1218-4-1 cells derived from embryonic stem cells and laboratoryderived cell lines of pre-implantation blastocyst-origin may, retain some immunological properties. It is true that, immune privilege provides protection to vital tissues or cells of the body when foreign antigens are introduced into these sites [176]. Moreover, variety of tissues and anatomical structures, including the hair follicles and mucosal surfaces, and sites of chronic inflammation and developing tumors may acquire immune privilege by recruiting immunoregulatory effector cells, but adult stem cells are no exception.…”

Section: Regeneration Of Immune Powermentioning

confidence: 99%

“…It proceeds and establishes immune cell reprogramming, and evokes difference between self and non-self substances. However, it is true that immune privilege can be developed to extend the capacity of adult and embryonic stem cells to display both relative and acquired immune function and to harness large therapeutic gain [176]. More specifically, embryonic stem cells and their differentiated tissue derivatives transplanted into a recipient do not necessarily have an ability to subvert immune responses to the extent required to exploit their pluripotency for regenerative medicine [176].…”

Section: Regeneration Of Immune Powermentioning

confidence: 99%

“…However, it is true that immune privilege can be developed to extend the capacity of adult and embryonic stem cells to display both relative and acquired immune function and to harness large therapeutic gain [176]. More specifically, embryonic stem cells and their differentiated tissue derivatives transplanted into a recipient do not necessarily have an ability to subvert immune responses to the extent required to exploit their pluripotency for regenerative medicine [176]. Therefore, a pre-implantation-stage embryo that derives from a totipotent stem cell (i.e., a fertilized oocyte) must be protected from maternal allo-rejection for successful implantation and development to occur, because so many factor work in simultaneous or in synchronizing way during regeneration and wound healing of tissues and organs.…”

Section: Regeneration Of Immune Powermentioning

confidence: 99%

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Role of regeneration in tissue repairing and therapies

Upadhyay¹

2015

J Regen Med Tissue Eng

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Present review article emphasizes role of regeneration mechanism in various tissues and its use in organ transplantation for wound healing and repairing. This article also explains uses of various stem cell types in transplantation technologies and its applications in regenerative medicine and therapeutics. This review also addresses tissue engineering methods and use of new biological scaffold materials and promising candidates such as immunomodulators, adhesions, integrins in tissue repairing and induction of regeneration in injured tissues. In addition, role of various molecules of immune cell system, gene cascades and transcription specific proteins (TSPs) and growth factors in formation of microenvironment for differentiation are also explained. Moreover, mechanism of regeneration in various tissues such as neural, skeletal, cardiac, muscular, adipose and gonadial tissues, and bone marrow is described in detail. This article also suggest an urgent need for development of new advanced methods, technologies, biomatrices, polymers and scaffold materials, and cell based therapies to overcome the problem of disable and injured patients. Hence, landmark innovations are required in the field of regenerative medicine, tissue engineering, and developmental biology for successful tissue repairing and organ transplants to serve the human society.

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chinmo Is a Functional Effector of the JAK/STAT Pathway that Regulates Eye Development, Tumor Formation, and Stem Cell Self-Renewal in Drosophila

Cited by 177 publications

References 74 publications

Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis

Role of regeneration in tissue repairing and therapies

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